1. Field of the Invention
The present invention relates to systems and methods used to determine the relative effectiveness of anti-cancer drugs on live cells from tissue, blood, and fluids, and more particularly to such systems and methods employing spectrophotometry to assess optical density of cells in response to treatments employing anti-cancer drugs.
2. Description of Related Art
Cell death may occur in a variety of manners, but successful anti-cancer drugs tend to cause death of cancer cells by the very specific process of apoptosis. Apoptosis is a mechanism by which a cell disassembles and packages itself for orderly disposal by the body. Apoptosis is commonly used by the body to discard cells when they are no longer needed, are too old, or have become damaged or diseased. In fact, some cells with dangerous mutations that might lead to cancer and even some early-stage cancerous cells may undergo apoptosis as a result of natural processes.
During apoptosis, the cell cuts and stores DNA, condenses the nucleus, discards excess water, and undergoes various changes to the cell membrane, such as blebbing, the formation of irregular bulges in the cell membrane. Apoptosis generally occurs after one of several triggers sends a signal to the cell that it should undergo apoptosis. In many cancer cells, this message system does not work correctly because the cell cannot detect the trigger, fails to send a signal properly after the trigger is received, or fails to act on the signal, or the cell may even have combinations of these problems. The overall effect is a resistance to undergoing apoptosis in some cancer cells.
Cancer, as used herein, includes epithelial malignancies, leukemia, lymphomas and mesenchymal malignancies. Many effective cancer drugs can induce a cancer cell to undergo apoptosis despite its resistance to the process. Accordingly, there is a need to detect whether a particular drug candidate can cause apoptosis in various types of cancer cells and also to determine the drug candidate's effectiveness as compared to other drugs or drug candidates. A complete analysis of effectiveness depends heavily upon automated processes for communicating with spectrophotometric equipment employed in the techniques, as well as appropriate data processing and display to users and others involved in the decision-making process of determining which drug is most suitable.
The MiCK assay, described in U.S. Pat. No. 6,077,684 and U.S. Pat. No. 6,258,553 is currently used to detect whether cancer cells from a patient undergo apoptosis in response to a particular drug known to be effective against one or more types of cancer. In the MiCK assay cancer cells from a patient are placed in a suspension of a given concentration of single cells or small cell clusters and allowed to adjust to conditions in multiple wells of a microtiter plate. Control solutions or solutions with various concentrations of known anti-cancer drugs, typically those drugs recommended for the patient's cancer type, are introduced into the wells with one test sample per well. The optical density of each well is then measured periodically, typically every few minutes, for a period of typically a few days. As a cell undergoes apoptosis-related blebbing, its optical density increases in a nearly linear fashion. If the cell does not undergo apoptosis or dies from other causes, its optical density does not change in this manner. Thus, if a plot of optical density (OD) v. time for a well yields a straight line curve having a positive slope over the time interval, then the anti-cancer drug in that well induces apoptosis of the patient's cancer cells and might be a suitable therapy for that patient. OD v. time data may also be used to calculate kinetic units, which similarly correlate with the suitability of a therapy for the patient.
The applicants also have a pending U.S. patent application related to the underlying technology, U.S. Publication No. 2011/0244503, as well as an international patent application, PCT/US2010/029318, whose entire disclosures are incorporated herein by reference.
In view of the benefits of the MiCK assay and its evolving technologies to patients, healthcare providers, and other participants in the oncology field, what is needed is a system and method for automating the determination of the relative effectiveness of anti-cancer drug candidates. As described below, these tests and their associated parameters, inventory control, recording keeping, shipment tracking, and communication with various persons can become a tedious and time-consuming affair. Therefore, as these techniques become more widely used, it is critical that most aspects of the process are automated using modern computer systems and software so the quick and accurate results can be analyzed and disseminated accordingly.